Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities.

Michael E Talkowski, Gilles Maussion, Liam Crapper, Jill A Rosenfeld, Ian Blumenthal, Carrie Hanscom, Colby Chiang, Amelia Lindgren, Shahrin Pereira, Douglas Ruderfer, Alpha B Diallo, Juan Pablo Lopez, Gustavo Turecki, Elizabeth S Chen, Carolina Gigek, David J Harris, Va Lip, Yu An, Marta Biagioli, Marcy E MacdonaldMichael Lin, Stephen J Haggarty, Pamela Sklar, Shaun Purcell, Manolis Kellis, Stuart Schwartz, Lisa G Shaffer, Marvin R Natowicz, Yiping Shen, Cynthia C Morton, James F Gusella, Carl Ernst

    Research output: Contribution to journalArticlepeer-review


    Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders.
    Original languageEnglish
    JournalAmerican Journal of Human Genetics
    Issue number6
    Publication statusPublished - 7 Dec 2012


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